Does infertility treatment cause ovarian cancer?

We are commonly asked if IVF increases the risk of ovarian cancer. Studies conducted over the past 20 years have tried to answer this question. A recent publication by van Leeuwen, et al., examined this issue carefully and produced some very interesting results.

What were the study basics?

The study published recently in Human Reproduction involved a very large retrospective analysis (data collected from the past) in the Netherlands of 25,152 infertile women (19,146 IVF and 6,006 non-IVF infertility patients) who received their infertility treatment between 1983 through 1995. The extensive follow-up period, which averaged about 15 years, made this study unique amongst others.

Why might infertility treatment result in ovarian cancer?

It has been theorized that the risk for ovarian cancer, which is estimated to be a 1/72-lifetime risk in the US, would increase because of ovarian stimulation and/or multiple ovulation sites forming across the surface of the ovary. Partially dispelling these concerns, this study did not show any increased risks for ovarian cancer for non-IVF infertile patients treated with either oral or injectable fertility medications. Also, further debunking the theory was the fact that the risk for ovarian cancer did not increase as the number of IVF cycles increased.

Is there something special about the IVF patient that increases her risk for ovarian cancer?

We also have wondered if the IVF patient simply has something wrong with her ovaries that predispose her to infertility, IVF treatments as well as ovarian/borderline ovarian cancer. The fact that there was a much larger percentage of “unexplained infertility” patients in the IVF-treated group suggests the IVF and non-IVF patient groups were indeed very different from each other.

Also understanding that borderline ovarian cancers normally make up only 20% of all ovarian cancers and are not anywhere as lethal as the more common ovarian cancers, it was somewhat unexpected to find that 46% of all ovarian cancers identified in the infertility patients in this study were borderline cancers. This high percentage of borderline lesions also suggests that something was unusual about the IVF-treated patient population.

What were some of the important findings in the study?

In reading this paper carefully, I was able to identify the following important points, some of which were not emphasized in the study:

Those IVF patients who never conceived were twice as likely to have any ovarian cancers and three times more likely to have borderline ovarian cancers.

In the study, the actual risk for any ovarian cancer by age 55 was estimated 1/141 (0.71%) in the IVF group compared to 1/222 (0.45%) for the normal population, an overall increased risk of 1/3rd but still a very rare event.

Also in the study, the actual risk for borderline ovarian cancer by age 55 was approximately 1/600 for the IVF patients compared to 1/1,200 for the general population, essentially doubling the risk. Still the actual incidence was still very, very rare.

What did we really learn from the study?

While I feel the authors did an amazing job collecting and analyzing the data, I felt the discussion section missed a few very important points:

Those that underwent IVF, especially unexplained infertility patients, may still differ in some way which may increase their risk for both prolonged infertility and ovarian/borderline ovarian cancers.

In other words, it may not be the IVF procedure itself as much as the underlying characteristics of the IVF patients, which predispose them to ovarian cancer risks.

Acute or chronic pelvic infections may very well increase the risk of borderline ovarian cancer.

The fact that IVF-treated patients were far more likely to have past pelvic infections may have been responsible for many of the findings described in this study. To the best of my knowledge, this has not been described before. Interestingly, chronic inflammation in other areas of the body also predisposes to some forms of cancer. Perhaps the pelvis is the same.

If one conceives through IVF, the risks for ovarian and borderline ovarian cancers drop to normal levels.

Either the pregnancy helps reduce the ovarian cancer risks or those who conceive are inherently at a reduced risk for ovarian cancer compared to those who never conceive.

This point has been found to be true with past studies that showed an increased risk of borderline ovarian cancers with the use of oral clomiphene citrate when used for more than 12 cycles without an eventual pregnancy. Once pregnancy occurred, even resulting in a miscarriage, the borderline ovarian cancer risks normalized (Rossing MA, et al. 1994).

Current regimens used to stimulate the ovaries are very different from those used prior to 1995.

The current risk factors could be better, worse or the same as those described in the study because IVF protocols have significantly changed since 1995.

In summary:

The risks for ovarian and borderline ovarian cancer for infertility patients undergoing IVF may be incrementally increased compared to the non-IVF population. Interestingly, far less lethal borderline ovarian cancers are found in a greater percentage in this very special patient population. Confounding factors, such as tubal factor infertility with acute/chronic infections, may increase the risk for ovarian malignancy in this patient population.

No matter how statistically significant the findings are, one still must note that the actual risks described in this study for women age 55 are still extraordinarily rare: 1/141 for any ovarian cancer and 1/600 for borderline ovarian cancers. These risks also are unlikely to deter a highly motivated infertility patient. Keep in mind that the average risk for a genetically abnormal child in IVF-treated patients is probably closer to 1/100, which is far higher than any of the risks for cancer listed in the current study. Let us all keep our perspective.

Still, we need to collect further data as many of the women in the study were only in their middle 50’s and the risks for ovarian cancer generally increase with age.

Above all, an IVF conception may very well reduce the ovarian cancer risks significantly. If conception never occurs, this may signal physicians to monitor the unsuccessful patients more carefully for future potential ovarian malignancies, although the actual incidence of the disease may still be quite rare.

Congratulations to the researchers who put an amazing amount of work into this study and we thank them for their dedication to infertile patients and to those of us who care so much for them.

I recently had the opportunity to be on Theresa Erickson's Internet radio show, Voice America. Known as the Surrogacy Lawyer, Theresa is renowned for her work on behalf of many patients faced with infertility looking for third party options. During my interview, we discussed the option of embryo donation from the physician, recipient and donor perspectives.

One of our donors, Tori, discussed her infertility experience as well as her and her husband's decision to donate their remaining embryos following a successful IVF procedure culminating in the delivery of her twins. You can see a picture of her twins and information regarding her amazing embryos by visiting our website.

Tori's Twins!

Tori and her husband decided that they wanted to “pay it forward” to other infertile couples. Here is a combination of her own words during the interview and some other comments she told me separately:

“Donating the embryos brought on a wide range of emotions; some expected such as the happiness to help another infertile couple, peace in setting the embryos ‘free’ by finally making a decision on their fate and others were a bit of a surprise such as a brief feeling of sheer panic that I ‘forgot’ something after leaving the clinic. The donation experience to me is like paying it forward to other infertile couples. I did not see any reason to leave the embryos suspended in time, did not want to see them destroyed and there was no reason to donate them to stem cell research when there are so many infertile couples in the world going through the same anguish I went through.

That feeling of anguish kept coming back, that longing and yearning for something that was so easy for others to have, yet so very difficult for me to obtain. I wanted to help someone relieve that awful feeling and by donating my embryos, I had a very good chance of doing just that.”

Tolisten to the show, please visit our Audio Gallery and click the play button to the right.

I am so thankful for people like Tori and other donors who consider giving their frozen embryos life while helping other people building their families at the same time. If you'd like more information on the process, please visit our embryo donation page on our Website, contact us at (239) 275-8118 or e-mail us at Fertility@DreamABaby.com.

Please stay tuned for the launching of our expanded embryo donation program called Embryo Donation International! I hope that many couples will consider to “pay it forward” just as Tori and her husband did.

Your thoughts and comments are always welcome.

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Did you see the new Jennifer Anniston movie, “The Switch” this weekend? What did you think about how it portrays the subject of infertility? Did you appreciate its humor or just find it way off base? If you didn’t see it, do you plan to? Share your thoughts!

After a year of trying to get pregnant naturally, 34-year-old Jaesen and her husband, 34-year-old Marco Petretta of Naples sought a medical consultation from Dr. Craig Sweet, a reproductive endocrinologist and director of Specialists in Reproductive Medicine & Surgery, P.A.

Following diagnostic testing, both husband and wife learned that they both had fertility problems. An ultrasound and blood work showed that Jaesen had a decreased ovarian reserve. This meant that Jaesen’s ovaries were likely to produce fewer eggs than most women her age, lowering the odds of success. In addition, a detailed sperm analysis showed that Marco had low sperm count and low motility (the sperm’s ability to move to the egg for fertilization). A scrotal ultrasound confirmed that Marco had a varicocele, a varicose vein of the testicle which is present in about 20 percent of infertile men. Following a minimally invasive procedure to embolize the vein, the couple discussed their treatment options with the goal of achieving a pregnancy.

Based on their diagnoses and Dr. Sweet’s recommendations, the couple opted for in vitro fertilization. During the process, Dr. Sweet retrieved only two eggs. Only one was mature. Next, the single egg was fertilized by injecting it with a single sperm. The single embryo continued to grow to the day five blastocyst stage at which point it was transferred into Jaesen’s uterus. With only one embryo produced during the process, their chances of pregnancy were slim.

Less than two weeks later, the couple learned they would become parents. On May 4, Jaesen gave birth to Vivienne Grace Petretta. The proud parents are looking forward to celebrating Marco’s first Father’s Day on June 20!